Solid Tumors, Adult
Conditions
Brief summary
The study will evaluate the safety, tolerability, and pharmacokinetics of intravenous DCR-PDL1 in adults with solid tumors. Participants will be enrolled in one of 4 ascending-dose cohorts. Each treatment cycle will consist of multiple intravenous (IV) doses. Dose escalation decisions will be based on data collected during the dose-limiting toxicity (DLT) period.
Interventions
DRUGDCR-PDL1
Solution for IV Infusion
Sponsors
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female adults, aged greater than or equal to (≥) 18 years. * Participants are required to have a documented, locally advanced or metastatic solid tumor malignancy, or non-Hodgkin's lymphoma * that is refractory to standard therapy known to provide clinical benefit for their condition OR * have demonstrated evidence of disease progression or relapse, via imaging, during or following standard therapy known to provide clinical benefit for their condition, OR * have demonstrated intolerance to standard therapy known to provide clinical benefit for their condition. OR * for which no standard therapy is available * Measurable disease according to RECIST version 1.1. * Malignancy not currently amenable to surgical intervention. * ECOG performance status of 0, 1, or 2, and an anticipated life expectancy of ≥ 3 months at the time of signing the informed consent. * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Participants with known CNS or leptomeningeal metastases not controlled by prior surgery or radiotherapy, or symptoms suggesting CNS involvement for which treatment is required. * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Change from Baseline in Physical Examination Findings: Cardiovascular, Respiratory, Gastrointestinal, and Neurological systems | Baseline to week 8 | A complete physical examination will include, at a minimum, assessments of the cardiovascular, respiratory, gastrointestinal, and neurological systems. |
| Change from Baseline in Urinalysis Parameter: Ketones and Nitrite | Baseline to week 8 | — |
| Change from Baseline in Urinalysis Parameter: Leukocyte esterase | Baseline to week 8 | — |
| Incidence and Nature of Adverse Events (AEs) | Baseline to week 8 | — |
| Incidence of Dose-limiting Toxicities (DLTs) | Baseline to week 8 | — |
| Change From Baseline in Vital Signs: Oral, Tympanic, Temporal Artery Temperature | Baseline up to week 8 | Vital signs will be measured in a semi-supine (i.e., semi-recumbent) position. |
| Change From Baseline in Vital Signs: Systolic and Diastolic Blood Pressure | Baseline up to week 8 | Vital signs will be measured in a semi-supine (i.e., semi-recumbent) position. |
| Change From Baseline in Vital Signs: Pulse and Respiratory Rate | Baseline up to week 8 | Vital signs will be measured in a semi-supine (i.e., semi-recumbent) position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. |
| Change from Baseline in 12-lead Electrocardiogram (ECG): Heart Rate and Pulse Rate | Baseline to week 8 | — |
| Change from Baseline in 12-lead Electrocardiogram (ECG): QRS intervals | Baseline to week 8 | ECG recordings will be made in a semi-supine (i.e., semi-recumbent) position, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. |
| Change from Baseline in 12-lead Electrocardiogram (ECG): QT intervals | Baseline to week 8 | ECG recordings will be made in a semi-supine (i.e., semi-recumbent) position, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. |
| Change from Baseline in 12-lead Electrocardiogram (ECG): QTcF intervals (QT Interval Corrected by the Fridericia Formula) | Baseline to week 8 | ECG recordings will be made in a semi-supine (i.e., semi-recumbent) position, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. |
| Change from Baseline in Hematology Parameter: Red blood cells, White blood cells, Lymphocytes, Monocytes, Eosinophils, Neutrophils, Basophils and Platelets, Reticulocytes | Baseline to week 8 | — |
| Change from Baseline in Hematology Parameter: Mean corpuscular volume (MCV) | Baseline to week 8 | — |
| Change from Baseline in Hematology Parameter: Mean corpuscular hemoglobin (MCH) | Baseline to week 8 | — |
| Change from Baseline in Hematology Parameter: Hemoglobin | Baseline to week 8 | — |
| Change from Baseline in Hematology Parameter: Hematocrit and Mean corpuscular hemoglobin concentration (MCHC) | Baseline to week 8 | — |
| Change from Baseline in Coagulation Parameter: International normalized ratio (INR) | Baseline to week 8 | — |
| Change from Baseline in Coagulation Parameter: Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) | Baseline to week 8 | — |
| Change from Baseline in Coagulation Parameter: Fibrinogen | Baseline to week 8 | — |
| Change from Baseline in Clinical Chemistry Parameter: Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma-glutamyl transferase (GGT), Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH) and Creatine kinase (CK) | Baseline to week 8 | — |
| Change from Baseline in Clinical Chemistry Parameter: Total protein and Albumin | Baseline to week 8 | — |
| Change from Baseline in Clinical Chemistry Parameter: Total bilirubin, Direct bilirubin, Fasting blood glucose, Creatinine and Blood urea nitrogen (BUN) | Baseline to week 8 | — |
| Change from Baseline in Clinical Chemistry Parameter: Sodium, Chloride and Potassium | Baseline to week 8 | — |
| Change from Baseline in Urinalysis Parameter: Glucose, Protein, Bilirubin and Urobilinogen | Baseline to week 8 | — |
| Change from Baseline in Urinalysis Parameter: Specific Gravity | Baseline to week 8 | — |
| Change from Baseline in Urinalysis Parameter: Potential of Hydrogen (pH) of Urine | Baseline to week 8 | — |
| Change from Baseline in Urinalysis Parameter: Blood | Baseline to week 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic Urine Concentrations of DCR-PDL1 | Up to 8 hours post-dose |
| Pharmacokinetic Plasma Concentrations of DCR-PDL1 | Pre-dose up to 48 hours post-dose |
Countries
United States
Contacts
Primary ContactNovo Nordisk
Outcome results
None listed